Lowe, Vanessa; Wisniewski, Laura; Sayers, Jacob; Evans, Ian; Frankel, Paul; Mercader-Huber, Nadia; Zachary, Ian C.; Pellet-Many, Caroline (2019). Neuropilin 1 mediates epicardial activation and revascularization in the regenerating zebrafish heart. Development, 146(13) Company of Biologists Limited 10.1242/dev.174482
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Unlike adult mammals, zebrafish can regenerate their heart. A key mechanism for regeneration is the activation of the epicardium, leading to the establishment of a supporting scaffold for new cardiomyocytes, angiogenesis and cytokine secretion. Neuropilins are co-receptors that mediate signaling of kinase receptors for cytokines with crucial roles in zebrafish heart regeneration. We investigated the role of neuropilins in response to cardiac injury and heart regeneration. All four neuropilin isoforms (nrp1a, nrp1b, nrp2a and nrp2b) were upregulated by the activated epicardium and an nrp1a-knockout mutant showed a significant delay in heart regeneration and displayed persistent collagen deposition. The regenerating hearts of nrp1a mutants were less vascularized, and epicardial-derived cell migration and re-expression of the developmental gene wt1b was impaired. Moreover, cryoinjury-induced activation and migration of epicardial cells in heart explants were reduced in nrp1a mutants. These results identify a key role for Nrp1 in zebrafish heart regeneration, mediated through epicardial activation, migration and revascularization.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy 04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy > Functional Anatomy |
UniBE Contributor: |
Mercader Huber, Nadia Isabel |
Subjects: |
600 Technology > 610 Medicine & health 500 Science > 570 Life sciences; biology |
ISSN: |
0950-1991 |
Publisher: |
Company of Biologists Limited |
Language: |
English |
Submitter: |
Nadia Isabel Mercader Huber |
Date Deposited: |
10 Dec 2019 14:59 |
Last Modified: |
05 Dec 2022 15:32 |
Publisher DOI: |
10.1242/dev.174482 |
PubMed ID: |
31167777 |
BORIS DOI: |
10.7892/boris.135529 |
URI: |
https://boris.unibe.ch/id/eprint/135529 |
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